Experimental Allergic Encephalomyelitis (EAE) is a cell-mediated, autoimmune and demyelinating disease of the central nervous system which is similar to Multiple Sclerosis in man. The major thrust of this research is to define the amino acid sequence which activates lymphocytes responsible for control and arrest of the demyelinating process. Previously, we reported that EAE may be prevented, suppressed or arrested by an antigen-specific and cyclophosphamide sensitive T lymphocyte subpopulation which we designated suppressor T lymphocytes (Ts). The development of Ts followed the administration of synthetic analogues of the disease-inducing determinants for rabbits, rats or guinea pigs. We now plan to further these studies of antigen-induced unresponsiveness to encephalitogenic challenge using specific determinants both for inducing and regulating EAE. And to define better the mechanism underlying EAE regulation. We propose, as a working hypothesis, that EAE regulation is mediated by a suppressor T lymphocyte subset that may be activated by a specific sequence, namely, the modified non-encephalitogenic sequence of the EAE-inducing determinant. To this end, we propose to synthesize a series of peptides made up of 1, 2, or 3 determinants known to induce EAE in one of 3 species. The sequence and position of these determinants mimics their respective locations in the parent MBP. Their ability to induce, regulate and/or potentiate either development or regulation of EAE in the Lewis rat will be documented by the results of this study. The successful completion of these studies is expected to provide a rational and direct approach for the control and arrest of similar demyelinating disease, such as Multiple Sclerosis in man.